Specific secretory granules of mammalian atrial cardiocytes contain peptides which possess natriuretic and diuretic activities in mammals, including man. One or more peptides have been called atrial natriuretic factor (ANF) or, interchangeably, atrial natriuretic peptide (ANP). In all mammals which have been studied ANF has a similar amino acid sequence but may differ in the amino acid composition at several positions. ANF has been identified as possessing several useful anti-angiotensinogenic properties. It is an effective vasodilator, natriuretic and diuretic agent as well as having other potential activities (as further discussed below).
Atrial natriuretic factor has been isolated from both human and animal sources, and its vasodilating, natriuretic and diuretic utility has been well documented. It has also been discovered that hypertensive humans and animals respond to injection of ANF to a much greater extent than do normotensive subjects. ANF has accordingly been considered potentially useful in treating hypertension and other diseases relating to a salt-water imbalance in the body. (These properties are summarized in review articles of two of the inventors herein, Dr. Johanne Tremblay and Dr. Pavel Hamet, published in "Medicographia" (1986) 8(3) and in "Nephrologie" (1987) 8:7-12).
ANF can be radioiodinated on tyrosine residues. U.S. Pat. No. 4,609,725 (Inventors: Brady, S. F. et al) which issued on Sep, 2, 1986, relates to atrial natriuretic factor and fragments thereof. Mono-iodinated-tyrosine derivatives of these peptides and fragments are described in this patent as being useful in the study of the metabolic half-life of ANF in clinical and in vitro studies.
It is known that ANF binding or uptake is tissue specific in the body. In particular, the renal glomeruli and the distal tubule of the nephron have specific binding sites (receptor sites) for ANF. Other organs which also selectively bind ANF include blood vessels, the lungs, the brain, the heart, the outer cortex and medulla of the adrenal gland, the liver and the gonads (see J. Genest and M. Cantin: The Artial Natriuretic Factor; its Physiology and Biochemistry, in Review of Physiology, Biochemistry and Pharmacology (Genest J., Cantin M. Eds), Springer-Verlag Heidelberg, Berlin, 1988). These target organs possess more ANF receptors or binding sites than other organs.
This selective binding of ANF to target organs in humans and other mammals could be useful in the identification and diagnosis of certain conditions and pathologies, and in identifying and diagnosing anomalies of target organs. It is known that ANF receptors are abnormal in the kidney during hypertension and diabetes (see, for example, Swithers, Stewart and McCarty, Life Sci. 40, 1673 (1987)) .